Long-acting Cabotegravir + Rilpivirine for HIV

(ATLAS-2M Trial)

Not currently recruiting at 141 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: ViiV Healthcare

Must be taking: Antiretrovirals

Must not be taking: Anticoagulants, Etravirine

Disqualifiers: Pregnancy, Hepatitis B, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new HIV treatment to determine if injections every eight weeks are as effective as those given every four weeks. It focuses on two drugs, cabotegravir and rilpivirine, administered as long-acting injections. Participants will either be new to this treatment or have already received it every four weeks. Ideal candidates have managed HIV with antiretroviral therapy and consistently maintain low virus levels in their blood. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, if you are on a standard HIV treatment, you need to have been on the same regimen for at least 6 months before joining the study. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the long-acting injectable forms of cabotegravir and rilpivirine are generally safe for adults. The FDA approved these injections for treating HIV, indicating a strong safety record. Studies have found that most people tolerate these injections well, whether administered every 4 or 8 weeks. Common side effects include mild to moderate pain at the injection site, headache, and fever, while serious side effects are rare.

The oral versions of cabotegravir and rilpivirine also maintain a good safety record. These tablets are used for short-term HIV treatment and are considered safe for patients whose virus is under control (meaning the virus is not actively reproducing). The side effects of the oral forms are similar to those of the injectables and are usually mild.

In summary, both the injectable and oral forms of cabotegravir and rilpivirine have demonstrated safety and tolerability in humans, based on previous research and FDA approval. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the long-acting combination of Cabotegravir and Rilpivirine for treating HIV because it offers a new delivery method that could improve patient convenience and adherence. Unlike standard daily oral treatments, such as the combination of tenofovir, emtricitabine, and efavirenz, these medications are administered as intramuscular injections every four or eight weeks. This long-acting formulation can reduce the need for daily pill-taking, which is a significant advantage for many patients. Additionally, by maintaining steady drug levels in the body over an extended period, it may enhance treatment effectiveness and reduce the chance of developing resistance.

What evidence suggests that this trial's treatments could be effective for HIV?

Studies have shown that the combination of cabotegravir and rilpivirine (CAB + RPV-LA) effectively controls the HIV virus. In this trial, participants will receive CAB + RPV-LA either once every 4 weeks or once every 8 weeks. Research indicates that this injectable treatment matches the effectiveness of daily pills in preventing the virus from growing in the body. Many patients prefer this method due to its reduced dosing frequency and greater convenience compared to daily pills. Long-term studies have demonstrated that CAB + RPV-LA remains effective over time. These findings suggest that CAB + RPV-LA is a reliable option for managing HIV. ^{6 7 8 9 10}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

ViiV Healthcare

Are You a Good Fit for This Trial?

Adults with HIV-1 who have maintained a viral load under 50 copies/mL and been on stable antiretroviral therapy for at least 6 months. Participants must understand the study commitments and be likely to complete them, not be pregnant or breastfeeding, and use effective contraception if of reproductive potential. Those with certain health conditions or taking specific medications are excluded.

Inclusion Criteria

I am not pregnant, not breastfeeding, and meet the fertility criteria.

Subjects enrolled in France must be affiliated to, or a beneficiary of, a social security category

I am on standard HIV-1 treatment and meet specific criteria for treatment history and viral load.

Exclusion Criteria

I need long-term blood thinners, with some exceptions.

I am allergic to the study drug or similar medications.

I don't have any health issues that would affect how my body handles the study medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Maintenance

Participants receive CAB LA + RPV LA every 4 or 8 weeks to evaluate efficacy, safety, and tolerability

48 weeks

Visits every 4 or 8 weeks

Extension

Participants may continue treatment beyond the main study period

Up to Week 100

Long-Term Follow-Up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cabotegravir Injectable Suspension
• Cabotegravir Tablets
• Rilpivirine Injectable Suspension
• Rilpivirine Tablets

Trial Overview The trial is testing the effectiveness of long-acting injections of Cabotegravir plus Rilpivirine given every two months compared to every month in controlling HIV-1. It includes adults previously treated with standard care or those already receiving these drugs monthly, assessing safety over a year.

How Is the Trial Designed?

Group I: Subjects in group 2 receiving study treatment once in 8 weeks Experimental Treatment 2 Interventions

Group 2 will consist of subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in Group 2 will be randomized to receive CAB LA plus RPV LA Q8W via IM route.

Group II: Subjects in group 2 receiving study treatment once in 4 weeks Experimental Treatment 2 Interventions

Group 2 will consist of subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in Group 2 will be randomized to continue CAB LA plus RPV LA Q4W administration via IM route.

Group III: Subjects in group 1 receiving study treatment once in 8 weeks Experimental Treatment 4 Interventions

Group 1 will consist of subjects randomized from current ART SOC therapy. Subjects in group 1 will be randomized to receive CAB LA plus RPV LA Q8W via IM route. All subjects will receive oral therapy with CAB 30 mg + RPV 25 mg once daily prior to randomization.

Group IV: Subjects in group 1 receiving study treatment once in 4 weeks Experimental Treatment 4 Interventions

Group 1 will consist of subjects randomized from current ART SOC therapy. Subjects in group 1 will be randomized to receive CAB LA plus RPV LA Q4W via intramuscular (IM) route. All subjects will receive oral therapy with CAB 30 mg + RPV 25 mg once daily prior to randomization.

Who Is Running the Clinical Trial?

ViiV Healthcare

Lead Sponsor

Trials

379

Recruited

479,000+

Founded

2009

Headquarters

London, England, UK

Known For

HIV Research

Top Products

- Tivicay (dolutegravir), - Triumeq (abacavir/dolutegravir/lamivudine), - Juluca (dolutegravir/rilpivirine), - Apretude (cabotegravir)

Dr. Harmony Garges

ViiV Healthcare

Chief Medical Officer

MD

Deborah Waterhouse

ViiV Healthcare

Chief Executive Officer since 2017

Bachelor's degree in Business Administration

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Janssen Research and Development

Collaborator

Trials

2

Recruited

1,200+

Published Research Related to This Trial

Cabotegravir and rilpivirine, as long-acting injectable therapy for HIV-1, have shown to be non-inferior to traditional oral triple-therapy in phase II and III trials, indicating their effectiveness as a treatment option.

Patients generally accept the 4-weekly or 8-weekly injections despite some experiencing injection-site reactions, but there are still important questions regarding missed doses, drug interactions, and the therapy's efficacy across different HIV-1 subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating cabotegravir/rilpivirine long-acting, injectable in the treatment of HIV infection: emerging data and therapeutic potential. Fernandez, C., van Halsema, CL.[2020]

In a Phase 2b study involving 97 adults living with HIV-1, the long-acting formulation of cabotegravir and rilpivirine (CAB+RPV) administered every 2 months successfully maintained virologic suppression, with no participants showing HIV-1 RNA levels above 50 copies/ml after 12 months.

The long-acting CAB+RPV treatment had a favorable safety profile, with no new safety concerns identified, and 88% of participants preferred this regimen over their previous daily oral treatment, indicating high treatment satisfaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting cabotegravir and rilpivirine for HIV-1 suppression: switch to 2-monthly dosing after 5 years of daily oral therapy. Mills, A., Richmond, GJ., Newman, C., et al.[2023]

Long-acting injectable cabotegravir-rilpivirine (CAB-RPV) significantly improves viral suppression rates in people with HIV who have adherence challenges, achieving 60% suppression at 3 months compared to only 13% with standard oral treatment.

In a model projecting outcomes over 3 years, CAB-RPV combined with supportive services is expected to lead to a 44% viral suppression rate and a life expectancy of 9.4 years, outperforming both standard oral treatments and those with additional support services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Projected Benefits of Long-Acting Antiretroviral Therapy in Nonsuppressed People With Human Immunodeficiency Virus Experiencing Adherence Barriers. Chen, W., Gandhi, M., Sax, PE., et al.[2023]

Long-acting injectable therapies, cabotegravir (CAB) and rilpivirine (RPV), have been shown to be as effective as traditional oral antiretroviral therapy (ART) for HIV-1, maintaining efficacy over 96 weeks in clinical trials with virologically suppressed adults.

CAB has also demonstrated effectiveness as a preexposure prophylaxis (PrEP) option, significantly reducing HIV infections compared to daily oral medication, indicating its potential for broader use in HIV prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV. Bares, SH., Scarsi, KK.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40604367/

Patient-reported outcomes in clinical trials assessing the ... Results: Findings reveal that CAB + RPV-LA maintains high levels of viral suppression comparable to daily ART while improving patient ...

2. academic.oup.com academic.oup.com/ofid/article/12/5/ofaf220/8116433

Clinical Outcomes and Perspectives of People With Human ... Participants receiving long-acting cabotegravir plus rilpivirine experienced high rates of virologic suppression and a low rate of ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02951052

NCT02951052 | Study Evaluating the Efficacy, Safety, and ... This study is designed to demonstrate the non-inferior antiviral activity of switching to a two drug CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1904398

Long-Acting Cabotegravir and Rilpivirine for Maintenance ... Monthly injections of long-acting cabotegravir and rilpivirine were noninferior to standard oral therapy for maintaining HIV-1 suppression.

5. viivhealthcare.com viivhealthcare.com/hiv-news-and-media/news/press-releases/2025/march/deliver-long-acting-injectable-hiv-innovation/

ViiV Healthcare continues to deliver long-acting injectable ... Long-term follow-up data from the real-world OPERA study will include CAB+RPV LA effectiveness in individuals through two years, as well as ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11213970/

Safety and pharmacokinetics of oral and long-acting ... The IMPAACT 2017 Cohort 1 study findings showed exposure concentrations of CAB-LA or RPV-LA, given every 4 or 8 weeks per the adult-dosing ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03299049

NCT03299049 | Efficacy, Safety and Tolerability Study of ... CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 mg/mL of GSK1265744 as free acid for administration by IM ...

8. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/guidelines/perinatal/safety-toxicity-arv-agents-integrase-inhibitors-cabotegravir-vocabria

Appendix B: Cabotegravir - Safety and Toxicity in Pregnancy Long-acting CAB and rilpivirine (RPV) (LA CAB/RPV) is FDA approved for HIV treatment. CAB-LA is FDA approved for HIV pre-exposure prophylaxis (PrEP). Human ...

9. academic.oup.com academic.oup.com/ofid/article/12/7/ofaf368/8173806

Optimizing the Use of Cabotegravir Plus Rilpivirine Long ... This review examines trial and real-world data on CAB + RPV-LA, addressing virological outcomes in relation to HIV subtype, archived resistance, body mass.

10. sciencedirect.com sciencedirect.com/science/article/pii/S2590059525000962

Long-Acting Cabotegravir and Rilpivirine Treatment for HIV ... Cabotegravir has been safely used in individuals with severe renal impairment. Oral dolutegravir (an INSTI) plus oral rilpivirine have been studied and deemed ...